Scleroderma or Systemic Sclerosis (SSc) is an autoimmune connective tissue disorder of unknown cause characterized by microvascular injury, excessive fibrosis of the skin, and distinctive visceral involvement including the heart, lung, kidneys and gastrointestinal tract. Scleroderma is a progressive condition in which fibrous tissue grows abnormally, causing the skin to thicken and harden, often disfiguring and disabling patients. It affects between 5,000-10,000 new persons annually (USA) and is associated with a high morbidity and a poor prognosis. Overall, scleroderma affects an estimated 300,000 Americans, most of them women.
Forty percent of all Scleroderma patients develop at least moderate restrictive lung disease. A high proportion of Scleroderma patients (80 percent) develop lung involvement, either interstitial lung disease and/or pulmonary hypertension, which are the leading causes of death due to Scleroderma. The mortality rate in Scleroderma patients with severe restrictive lung disease is about 30 percent within 10 years of onset.
The statistics underscore the need for effective treatment, preferably at an early stage in the illness, to prevent progression to severe interstitial lung disease. SSc is treated with oral medications to halt the progression of disease. These drugs include cyclophosphamide, high dose prednisolone or even stem cell transplantation, all having severe side effects. In SSc, also drugs that improve circulation, promote gastrointestinal function, preserve kidney function, and control high blood pressure are given. Cyclophophamide is an anti-cancer drug that suppresses the immune system. This is the first drug that has been proven to alleviate the most devastating effects of SSc. Patients taking cyclophosphamide had a significant improvement in lung function and a reduction in breathlessness.
Although many research groups work on the unraveling of SSc pathogenesis, to date, the exact pathways underlying the pathogenesis of SSc remain unknown. Currently most of the research is focused on the underlying pathways that cause fibroblast activation. A deregulated growth and activation of fibroblasts has often suggested to be implicated in SSc. However, a mode of action that is responsible for this ongoing fibroblasts activation has not been identified.